Internationally, there are 31 million HIV-infected individuals and 11 million people have already died from AIDS. A major focus within our laboratory has been to define the unique epidemiologic, clinical, virologic, and immunologic features of HIV-1 and HIV-2 infections in developing countries and in the U.S. In a multicenter study on perinatal transmission in the U.S., we determined that elevated RNA viral levels at birth were suggestive of in utero infection and that a high plasma RNA viral load in the first two months of life (< 300,000 copies per ml) was strongly associated with rapid progression to AIDS or death. None of the infants with < 70,000 copies/ml progressed to AIDS, suggesting that antiretroviral therapy in infants with high viral loads should result in improved survival and delayed progression We subsequently studied maternal HIV RNA levels, which were found to be highly predictive of risk of perinatal transmission. For example, transmission rates increased from 0% to 40% for mothers with RNA levels < 1,000 to over 100,000 copies/ml. The highest risk of transmission occurred in women with RNA levels < 100,000 copies/ml who were not on zidovudine (63% transmission). Maternal viral load was the strongest of four independent predictors of transmission risk that included zidovudine use, duration of ruptured membranes greater than 4 hours, and birth weight < 2500 g. In addition, co-infection of the mother with HIV and hepatitis C virus resulted in a threefold increase in perinatal transmission of HCV and a twofold increase in perinatal transmission of HIV. In Pune, India, we have screened 8,134 patients attending STD clinics, of whom 23% are HIV positive. In a prospective study the incidence rate was 16.2% among female sex workers, 7.4% among men and 6.6% among married spouses of these men. The high frequency of multiple STDs and HIV infection coupled with low condom use and low AIDS awareness emphasizes the rapid spread of HIV into both high and lower risk populations in India. Among 3,874 HIV antibody-negative persons, 58 were p24 antigen positive and subsequently seroconverted. Unprotected sexual contact with a commercial sex worker in the presence of an active genital ulcer at the time of screening were significantly associated with seroconversion. Signs and symptoms independently associated with p24 antigenemia included fever, arthralgias, and night sweats. Thus, screening for p24 antigen in HIV antibody-negative persons was found to be a reliable and effective method for determining recent risk behavior and identifying clinical signs of acute primary HIV infection. Studies on HIV viral load demonstrated that at the time of an acute opportunistic infection, HIV RNA may increase three to fivefold, which subsequently declines to the baseline viral RNA level 3 months following successful treatment. The changes in viral RNA correlated best with changes in cytokines associated with immune activation. In a community-based STD mass treatment campaign of 14,000 individuals in Uganda, there was a 60% in reduction in the prevalence and incidence of bacterial STDs, but the incidence of HIV infection was unaffected. Additional future studies will address the effect of mass treatment of STDs during pregnancy on perinatal outcomes including the correlation.